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Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition
BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplan...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929774/ https://www.ncbi.nlm.nih.gov/pubmed/27364362 http://dx.doi.org/10.1186/s12967-016-0954-1 |
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author | Yuan, Dongdong Su, Guangjie Liu, Yue Chi, Xinjin Feng, Jiayu Zhu, Qianqian Cai, Jun Luo, Gangjian Hei, Ziqing |
author_facet | Yuan, Dongdong Su, Guangjie Liu, Yue Chi, Xinjin Feng, Jiayu Zhu, Qianqian Cai, Jun Luo, Gangjian Hei, Ziqing |
author_sort | Yuan, Dongdong |
collection | PubMed |
description | BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplantation-induced ALI and whether its underlying mechanism was relative with connexin43 (Cx43) alternation. The authors postulated that endotoxin induced enhancement of Cx43 gap junction (GJ) plays a critical role in mediating post liver transplantation ALI and that pretreatment with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. METHODS: Male Sprague–Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx43 inhibitor, enanthol (0.1 mg/kg) and propofol (50 mg/kg), a commonly used anesthetic in clinical anesthesia. In vitro study, BEAS-2B cells, a kind of lung epithelial cell line expressing Cx43, exposed to lipopolysaccharide (LPS), which mainly contributed to ALI. Function of Cx43 GJ was regulated by Cx43 specific inhibitors, gap26 (300 μM) or enhancer, retinoic acid (10 μM) and two specific siRNAs. RESULTS: Compared with the sham group, AOLT results in ALI obviously with plasma endotoxin increase. Cx43 inhibition decreased ALI through inflammatory reaction reduction. In vitro studies, LPS-induced BEAS-2B cells damage was attenuated by Cx43 function inhibition, but amplified by enhancement. Another important finding was propofol reduced Cx43 function and protected against LPS-mediated BEAS-2B cells damage or AOLT-induced ALI, mechanisms of which were also associated with inflammatory reaction decrease. CONCLUSION: Cx43 plays a vital role in liver transplantation-induced ALI. Propofol decreased Cx43 function and protected against ALI in vivo and in vitro. This finding provide a new basis for targeted intervention of organ protection in liver transplantation, even in other kinds of operations. |
format | Online Article Text |
id | pubmed-4929774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49297742016-07-02 Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition Yuan, Dongdong Su, Guangjie Liu, Yue Chi, Xinjin Feng, Jiayu Zhu, Qianqian Cai, Jun Luo, Gangjian Hei, Ziqing J Transl Med Research BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplantation-induced ALI and whether its underlying mechanism was relative with connexin43 (Cx43) alternation. The authors postulated that endotoxin induced enhancement of Cx43 gap junction (GJ) plays a critical role in mediating post liver transplantation ALI and that pretreatment with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. METHODS: Male Sprague–Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx43 inhibitor, enanthol (0.1 mg/kg) and propofol (50 mg/kg), a commonly used anesthetic in clinical anesthesia. In vitro study, BEAS-2B cells, a kind of lung epithelial cell line expressing Cx43, exposed to lipopolysaccharide (LPS), which mainly contributed to ALI. Function of Cx43 GJ was regulated by Cx43 specific inhibitors, gap26 (300 μM) or enhancer, retinoic acid (10 μM) and two specific siRNAs. RESULTS: Compared with the sham group, AOLT results in ALI obviously with plasma endotoxin increase. Cx43 inhibition decreased ALI through inflammatory reaction reduction. In vitro studies, LPS-induced BEAS-2B cells damage was attenuated by Cx43 function inhibition, but amplified by enhancement. Another important finding was propofol reduced Cx43 function and protected against LPS-mediated BEAS-2B cells damage or AOLT-induced ALI, mechanisms of which were also associated with inflammatory reaction decrease. CONCLUSION: Cx43 plays a vital role in liver transplantation-induced ALI. Propofol decreased Cx43 function and protected against ALI in vivo and in vitro. This finding provide a new basis for targeted intervention of organ protection in liver transplantation, even in other kinds of operations. BioMed Central 2016-06-30 /pmc/articles/PMC4929774/ /pubmed/27364362 http://dx.doi.org/10.1186/s12967-016-0954-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Yuan, Dongdong Su, Guangjie Liu, Yue Chi, Xinjin Feng, Jiayu Zhu, Qianqian Cai, Jun Luo, Gangjian Hei, Ziqing Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
title | Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
title_full | Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
title_fullStr | Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
title_full_unstemmed | Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
title_short | Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
title_sort | propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929774/ https://www.ncbi.nlm.nih.gov/pubmed/27364362 http://dx.doi.org/10.1186/s12967-016-0954-1 |
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